P19971 (TYPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thymidine phosphorylase
Short name=TP
EC=2.4.2.4

Alternative name(s):
Gliostatin
Platelet-derived endothelial cell growth factor
Short name=PD-ECGF
TdRPase

Gene names

Name:	TYMP
Synonyms:	ECGF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	482 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro. Ref.7 Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis. Ref.7
Catalytic activity	Thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate.
Pathway	Pyrimidine metabolism; dTMP biosynthesis via salvage pathway; dTMP from thymine: step 1/2.
Subunit structure	Homodimer.
Involvement in disease	Defects in TYMP are the cause of mitochondrial DNA depletion syndrome type 1 (MTDPS1) [MIM:603041]; also known as myoneurogastrointestinal encephalomyopathy. A multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, thin body habitus, peripheral neuropathy, and myopathy. Ref.8 Ref.9
Sequence similarities	Belongs to the thymidine/pyrimidine-nucleoside phosphorylase family.

Ontologies

Keywords
Biological process	Angiogenesis Chemotaxis Differentiation
Coding sequence diversity	Polymorphism
Disease	Disease mutation Progressive external ophthalmoplegia
Domain	Repeat
Molecular function	Developmental protein Glycosyltransferase Growth factor Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	DNA replication Traceable author statement. Source: ProtInc angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW chemotaxis Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial genome maintenance Traceable author statement. Source: ProtInc pyrimidine base metabolic process Traceable author statement. Source: Reactome pyrimidine nucleoside catabolic process Traceable author statement. Source: Reactome pyrimidine nucleoside salvage Traceable author statement. Source: Reactome pyrimidine nucleotide metabolic process Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW platelet-derived growth factor receptor binding Traceable author statement. Source: ProtInc pyrimidine-nucleoside phosphorylase activity Inferred from electronic annotation. Source: InterPro thymidine phosphorylase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 10

10

PRO_0000035874

Chain

11 – 482

472

Thymidine phosphorylase

PRO_0000035875

Regions

Repeat

265 – 279

15

R-V-A-A-A-L-X(5,6)-L-G-R

Repeat

329 – 342

14

R-V-A-A-A-L-X(5,6)-L-G-R

Repeat

393 – 401

9

R-A-L-X-X-A-L-V-L

Repeat

453 – 461

9

R-A-L-X-X-A-L-V-L

Natural variations

Natural variant

44

1

R → Q in MTDPS1. Ref.9

VAR_016777

Natural variant

145

1

G → R in MTDPS1. Ref.8

VAR_007643

Natural variant

153

1

G → S in MTDPS1. Ref.8

VAR_007644

Natural variant

222

1

K → R in MTDPS1. Ref.8

VAR_007645

Natural variant

289

1

E → A in MTDPS1. Ref.8

VAR_007646

Natural variant

397 – 398

2

Missing in MTDPS1.

VAR_007647

Natural variant

471

1

S → L. Ref.1 Ref.4
Corresponds to variant rs11479 [ dbSNP | Ensembl ].

VAR_007648

Experimental info

Sequence conflict

195

1

D → E in AAH18160. Ref.4

Secondary structure

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482

Helix Strand Turn

Details...

Helix

36 – 44

9

Helix

51 – 63

13

Helix

68 – 81

14

Helix

85 – 96

12

Helix

106 – 111

6

Beta strand

112 – 118

7

Helix

125 – 134

10

Turn

135 – 137

3

Beta strand

139 – 143

5

Helix

154 – 158

5

Helix

170 – 180

11

Beta strand

181 – 185

5

Beta strand

189 – 192

4

Helix

193 – 204

12

Helix

211 – 224

14

Beta strand

228 – 236

9

Helix

245 – 261

17

Beta strand

266 – 272

7

Beta strand

280 – 283

4

Helix

284 – 294

11

Helix

300 – 316

17

Helix

323 – 335

13

Helix

338 – 349

12

Helix

354 – 362

9

Helix

365 – 371

7

Beta strand

376 – 382

7

Beta strand

387 – 392

6

Helix

394 – 405

12

Beta strand

420 – 423

4

Beta strand

436 – 446

11

Helix

449 – 458

10

Beta strand

459 – 464

6

Beta strand

475 – 477

3

Sequences

	Sequence		Length	Mass (Da)
	P19971 [UniParc]. Last modified June 7, 2005. Version 2. Checksum: 0652FA0B8F3BDE28	FASTA	482	49,955
	10 20 30 40 50 60 MAALMTPGTG APPAPGDFSG EGSQGLPDPS PEPKQLPELI RMKRDGGRLS EADIRGFVAA 70 80 90 100 110 120 VVNGSAQGAQ IGAMLMAIRL RGMDLEETSV LTQALAQSGQ QLEWPEAWRQ QLVDKHSTGG 130 140 150 160 170 180 VGDKVSLVLA PALAACGCKV PMISGRGLGH TGGTLDKLES IPGFNVIQSP EQMQVLLDQA 190 200 210 220 230 240 GCCIVGQSEQ LVPADGILYA ARDVTATVDS LPLITASILS KKLVEGLSAL VVDVKFGGAA 250 260 270 280 290 300 VFPNQEQARE LAKTLVGVGA SLGLRVAAAL TAMDKPLGRC VGHALEVEEA LLCMDGAGPP 310 320 330 340 350 360 DLRDLVTTLG GALLWLSGHA GTQAQGAARV AAALDDGSAL GRFERMLAAQ GVDPGLARAL 370 380 390 400 410 420 CSGSPAERRQ LLPRAREQEE LLAPADGTVE LVRALPLALV LHELGAGRSR AGEPLRLGVG 430 440 450 460 470 480 AELLVDVGQR LRRGTPWLRV HRDGPALSGP QSRALQEALV LSDRAPFAAP SPFAELVLPP QQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor." Ishikawa F., Miyazono K., Hellman U., Drexler H., Wernstedt C., Hagiwara K., Usuki K., Takaku F., Risau W., Heldin C.-H. Nature 338:557-562(1989) [PubMed: 2467210] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT LEU-471. Tissue: Placenta.
[2]	"Expression of recombinant platelet-derived endothelial cell growth factor in the yeast Saccharomyces cerevisiae." Finnis C., Goodey A., Courtney M., Sleep D. Yeast 8:57-60(1992) [PubMed: 1580101] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-471. Tissue: Brain and Lung.
[5]	"Angiogenic factor." Furukawa T., Yoshimura A., Sumizawa T., Haraguchi M., Akiyama S., Fukui K., Yamada Y. Nature 356:668-668(1992) [PubMed: 1570012] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 149-244, PROTEIN SEQUENCE OF 125-178 AND 236-244.
[6]	"Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor." Asai K., Nakanishi K., Isobe I., Eksioglu Y.Z., Hirano A., Hama K., Miyamoto T., Kato T. J. Biol. Chem. 267:20311-20316(1992) [PubMed: 1400349] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[7]	"Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity." Usuki K., Saras J., Waltenberger J., Miyazono K., Pierce G., Thomason A., Heldin C.-H. Biochem. Biophys. Res. Commun. 184:1311-1316(1992) [PubMed: 1590793] [Abstract] Cited for: FUNCTION.
[8]	"Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder." Nishino I., Spinazzola A., Hirano M. Science 283:689-692(1999) [PubMed: 9924029] [Abstract] Cited for: VARIANTS MTDPS1 ARG-145; SER-153; ARG-222; ALA-289 AND 397-LEU-ALA-398 DEL.
[9]	"Phenotypic variability in a Spanish family with MNGIE." Gamez J., Ferreiro C., Accarino M.L., Guarner L., Tadesse S., Marti R.A., Andreu A.L., Raguer N., Cervera C., Hirano M. Neurology 59:455-457(2002) [PubMed: 12177387] [Abstract] Cited for: VARIANT MTDPS1 GLN-44.
+	Additional computationally mapped references.

Web resources

R&D Systems' cytokine mini-reviews: PD-ECGF

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M63193 mRNA. Translation: AAA60043.1.
U62317 Genomic DNA. Translation: AAB03344.2.
BC018160 mRNA. Translation: AAH18160.1.
BC052211 mRNA. Translation: AAH52211.1.

IPI

IPI00292858.

PIR

S03904.

RefSeq

NP_001107227.1. NM_001113755.1.
NP_001107228.1. NM_001113756.1.
NP_001944.1. NM_001953.3.

UniGene

Hs.592212.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UOU	X-ray	2.11	A	12-482	[»]
2J0F	X-ray	2.31	A/B/C/D	1-482	[»]
2WK5	X-ray	2.99	A/B/C/D	1-482	[»]
2WK6	X-ray	2.50	A/B	1-482	[»]

ProteinModelPortal

P19971.

SMR

P19971. Positions 32-479.

ModBase

Search...

Protein-protein interaction databases

IntAct

P19971. 1 interaction.

STRING

P19971.

PTM databases

PhosphoSite

P19971.

Polymorphism databases

DMDM

67477361.

2D gel databases

OGP

P19971.

Proteomic databases

PRIDE

P19971.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000252029; ENSP00000252029; ENSG00000025708.
ENST00000395678; ENSP00000379036; ENSG00000025708.
ENST00000395680; ENSP00000379037; ENSG00000025708.

GeneID

1890.

KEGG

hsa:1890.

UCSC

uc003bmb.2. human.

Organism-specific databases

CTD

1890.

GeneCards

GC22M050964.

H-InvDB

HIX0016616.

HGNC

HGNC:3148. TYMP.

HPA

CAB002518.
HPA001072.

MIM

131222. gene.
603041. phenotype.

neXtProt

NX_P19971.

Orphanet

298. Myoneurogastrointestinal encephalopathy syndrome.

PharmGKB

PA153.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15774.

GeneTree

ENSGT00390000009250.

HOVERGEN

HBG000082.

OrthoDB

EOG4DJJWP.

PhylomeDB

P19971.

Enzyme and pathway databases

BRENDA

2.4.2.4. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P19971.

Bgee

P19971.

CleanEx

HS_TYMP.

Genevestigator

P19971.

GermOnline

ENSG00000025708. Homo sapiens.

Family and domain databases

InterPro

IPR000312. Glycosyl_Trfase_fam3.
IPR017459. Glycosyl_Trfase_fam3_N.
IPR020072. Glycosyl_Trfase_fam3_subgr_N.
IPR013102. PYNP_C.
IPR018090. Pyrmidine_PPas_bac/euk.
IPR000053. Pyrmidine_PPase.
IPR017872. Pyrmidine_PPase_CS.
[Graphical view]

Gene3D

G3DSA:3.90.1170.30. G3DSA:3.90.1170.30. 1 hit.
G3DSA:1.20.970.10. Glyco_trans_3. 1 hit.
G3DSA:3.40.1030.10. Glyco_trans_3. 1 hit.

KO

K00758.

PANTHER

PTHR10515. Pyrmidine_PPase. 1 hit.

Pfam

PF02885. Glycos_trans_3N. 1 hit.
PF00591. Glycos_transf_3. 1 hit.
PF07831. PYNP_C. 1 hit.
[Graphical view]

PIRSF

PIRSF000478. TP_PyNP. 1 hit.

SMART

SM00941. PYNP_C. 1 hit.
[Graphical view]

SUPFAM

SSF47648. Glyco_trans_3. 1 hit.
SSF52418. Glyco_trans_3. 1 hit.
SSF54680. PYNP_C. 1 hit.

TIGRFAMs

TIGR02644. Y_phosphoryl. 1 hit.

PROSITE

PS00647. THYMID_PHOSPHORYLASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01101. Capecitabine.
DB01248. Docetaxel.
DB00322. Floxuridine.
DB00544. Fluorouracil.
DB00795. Sulfasalazine.
DB00675. Tamoxifen.

NextBio

7707.

SOURCE

Search...

Entry information

Entry name

TYPH_HUMAN

Accession

Primary (citable) accession number: P19971
Secondary accession number(s): A8MW15, Q13390, Q8WVB7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	June 7, 2005
Last modified:	January 25, 2012
This is version 145 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.